OBJECTIVE: To correlate changes in serum levels of intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases (MMP) with clinical and MRI evidence of disease activity in MS patients receiving treatment with interferon-beta (rIFNbeta)-1b. BACKGROUND: rIFNbeta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechanism of action on improving the integrity of the blood-brain barrier remains unclear. METHODS: sICAM-1 and MMP-9 and MMP-2 serum levels were longitudinally (24 months) investigated (ELISA; zymography) in correlation with the modifications of the integrated area under the curve of Expanded Disability Status Scale scores normalized to entry baseline (deltaEDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNbeta-1b production (MxA) in 36 RRMS patients. RESULTS: During the first 12 months of treatment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 were significantly negatively correlated. MMP-2 levels did not change significantly during the same period. During the second semester of the study, deltaEDSS AUC was significantly reduced. The percentage of patients with Gd+ MRI decreased significantly in the first (33%), second (29%), third (20%), and fourth (28%) semesters of treatment compared to baseline (62%). The NAB+ patients (14%) tended to have lower sICAM-1 levels at the ninth month; a higher MMP-9 activity at the sixth, 12th, and 18th months; and a greater deltaEDSS AUC in the third semester of treatment in comparison with the NAB- patients. CONCLUSIONS: These results show that rIFNbeta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.
OBJECTIVE: To correlate changes in serum levels of intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases (MMP) with clinical and MRI evidence of disease activity in MS patients receiving treatment with interferon-beta (rIFNbeta)-1b. BACKGROUND: rIFNbeta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechanism of action on improving the integrity of the blood-brain barrier remains unclear. METHODS: sICAM-1 and MMP-9 and MMP-2 serum levels were longitudinally (24 months) investigated (ELISA; zymography) in correlation with the modifications of the integrated area under the curve of Expanded Disability Status Scale scores normalized to entry baseline (deltaEDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNbeta-1b production (MxA) in 36 RRMS patients. RESULTS: During the first 12 months of treatment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 were significantly negatively correlated. MMP-2 levels did not change significantly during the same period. During the second semester of the study, deltaEDSS AUC was significantly reduced. The percentage of patients with Gd+ MRI decreased significantly in the first (33%), second (29%), third (20%), and fourth (28%) semesters of treatment compared to baseline (62%). The NAB+ patients (14%) tended to have lower sICAM-1 levels at the ninth month; a higher MMP-9 activity at the sixth, 12th, and 18th months; and a greater deltaEDSS AUC in the third semester of treatment in comparison with the NAB- patients. CONCLUSIONS: These results show that rIFNbeta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.
Authors: Elizabeth Milward; Kee Jun Kim; Arek Szklarczyk; Thien Nguyen; Giorgia Melli; Mamatha Nayak; Deepa Deshpande; Chantel Fitzsimmons; Ahmet Hoke; Douglas Kerr; John W Griffin; Peter A Calabresi; Katherine Conant Journal: J Neuroimmunol Date: 2007-12-11 Impact factor: 3.478
Authors: Patricia L Musolino; Yi Gong; Juliet M T Snyder; Sandra Jimenez; Josephine Lok; Eng H Lo; Ann B Moser; Eric F Grabowski; Matthew P Frosch; Florian S Eichler Journal: Brain Date: 2015-09-15 Impact factor: 13.501
Authors: L Shinto; G Marracci; S Baldauf-Wagner; A Strehlow; V Yadav; L Stuber; D Bourdette Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2009-01-25 Impact factor: 4.006
Authors: A Bertolotto; S Malucchi; A Sala; G Orefice; P B Carrieri; M Capobianco; E Milano; F Melis; M T Giordana Journal: J Neurol Neurosurg Psychiatry Date: 2002-08 Impact factor: 10.154
Authors: Isobel A Scarisbrick; Rachel Linbo; Alexander G Vandell; Mark Keegan; Sachiko I Blaber; Michael Blaber; Diane Sneve; Claudia F Lucchinetti; Moses Rodriguez; Eleftherios P Diamandis Journal: Biol Chem Date: 2008-06 Impact factor: 3.915